Género y Personas sin hogar. La doble invisibilidad

Las personas sin hogar son un colectivo prácticamente invisible en nuestra sociedad y si a esto le añades que esa persona sea mujer, nos encontramos frente a una doble invisibilidad. Ante esta problemática, nos planteamos esta investigación para poder acercarnos a la realidad de las mujeres sin hogar y poder hacer más visible su situación

Towards near-threshold server processors

The popularity of cloud computing has led to a dramatic increase in the number of data centers in the world. The ever-increasing computational demands along with the slowdown in technology scaling has ushered an era of power-limited servers. Techniques such as near-threshold computing (NTC) can be used to improve energy efficiency in the post-Dennard scaling era. This paper describes an architecture based on the FD-SOI process technology for near-threshold operation in servers. Our work explores the trade-offs in energy and performance when running a wide range of applications found in private and public clouds, ranging from traditional scale-out applications, such as web search or media streaming, to virtualized banking applications. Our study demonstrates the benefits of near-threshold operation and proposes several directions to synergistically increase the energy proportionality of a near-threshold server

Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple‐negative breast cancer

Cell cycle; Gene expression; Triple-negative breast cancerCiclo celular; Expresión génica; Cáncer de mama triple negativoCicle cel·lular; Expressió gènica; Càncer de mama triple negatiuTriple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B‐MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co‐inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4‐MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.We thank the CRG genomics unit, the CRG‐UPF flow cytometry unit, and the VHIO mouse facility for their contribution. We thank Pharmaxis for the supply of PXS LOXL2 inhibitors. SS is supported by the Plan Estatal de I + D + I (COMBAT PID2019‐110598GA‐I00), and the ERC Starting Grant (ERC‐StG‐852343‐EPICAMENTE). LP‐R is supported by the Juan de la Cierva‐Formación fellowship (FJC2019‐040598‐I) and Fundación Franscico Cobos fellowship. TVT is supported by Plan Estatal de I + D + I (PID2019‐108008RJ‐I00), AECC (INVES20036TIAN), and a Ramón y Cajal investigator contract (RYC2020‐029098‐I). DC is supported by the la Caixa Foundation PhD fellowship (ID 100010434; fellowship code LCF/BQ/DI19/11730061)

Identification and validation of circulating miRNAs as endogenous controls in obstructive sleep apnea

microRNAs (miRNAs) are non-coding RNAs highly relevant as biomarkers for disease. A seminal study that explored the role of miRNAs in obstructive sleep apnea syndrome (OSA) demonstrated their usefulness in clinical management. Nevertheless, the miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in OSA. The objective of the study is to identify miRNAs that can be used as ECs in OSA. We evaluated 100 patients divided into two different cohorts: a learning cohort of 10 non-OSA and 30 OSA patients, and a validation cohort (20 non-OSA and 40 OSA patients). In the learning cohort, a profile of 188 miRNAs was determined in plasma by TaqMan Low Density Array. The best EC candidates were identified by mean center+SD normalization and concordance correlation restricted normalization. The results were validated using NormFinder and geNorm to assess the stability of those ECs. Eight miRNAs were identified as EC candidates. The combination miRNA-106a/miRNA-186 was identified as the most stable among all candidates. We identified a set of ECs to be used in the determination of circulating miRNA in OSA that may contribute to the homogeneity of results.The project is supported by PI 14/01266 and PI 18/00449 from the Instituto de Salud Carlos III (ISCIII), Fondo Europeo de Desarrollo Regional (FEDER), Sociedad Española de Neumología y Cirugía Torácica (SEPAR) and Societat Catalana de Pneumologia (SOCAP). The work is supported by IRBLleida Biobank (B.0000682) and PLATAFORMA BIOBANCOS PT17/0015/0027”. We thank all the investigators of Sleep Unit of Santa Maria Hospital. F.S.-M. is the recipient of a predoctoral fellowship from “AGAUR-University of Lleida” and Convocatòria d’Ajuts 2018 de Promoció a la Recerca en Salut. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Synergistic effect of antimetabolic and chemotherapy drugs in triple-negative breast cancer

The triple-negative breast cancer (TNBC) subtype comprises approximately 15% of all breast cancers and is associated with poor long-term outcomes. Classical chemotherapy remains the standard of treatment, with toxicity and resistance being major limitations. TNBC is a high metabolic group, and antimetabolic drugs are effective in inhibiting TNBC cell growth. We analyzed the combined effect of chemotherapy and antimetabolic drug combinations in MDA-MB-231, MDA-MB-468 and HCC1143 human TNBC cell lines. Cells were treated with each drug or with drug combinations at a range of concentrations to establish the half-maximal inhibitory concentrations (IC50). The dose-effects of each drug or drug combination were calculated, and the synergistic or antagonistic effects of drug combinations were defined. Chemotherapy and antimetabolic drugs exhibited growth inhibitory effects on TNBC cell lines. Antimetabolic drugs targeting the glycolysis pathway had a synergistic effect with chemotherapy drugs, and antiglycolysis drug combinations also had a synergistic effect. The use of these drug combinations could lead to new therapeutic strategies that reduce chemotherapy drug doses, decreasing their toxic effect, or that maintain the doses but enhance their efficacy by their synergistic effect with other drugsMaría I. Lumbreras-Herrera and Andrea Zapater-Moros are supported by Consejería de Educación e Investigación de la Comunidad de Madrid (IND2018/BMD-9262). Elena López-Camacho is supported by the Spanish Economy and Competitiveness Ministry (PTQ2018–009760). This work is supported by an unrestricted grant from Roch

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome

Introduction: Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS. Methods: Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components. Results: From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events. Conclusion: A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS.Instituto de Salud Carlos III (ISCIII; PI10/02763, PI10/02745, PI18/00449, and PI19/00907), co-funded by FEDER, “Una manera de hacer europa,” IRBLleida – Fundació Pifarré, CERCA Programme/Generalitat de Catalunya, SEPAR, ResMed Ltd. (Australia), Esteve-Teijin (Spain), Oxigen Salud (Spain), Associació Lleidatana de Respiratori (ALLER), and Sociedad Española de Sueño (SES). AZ is the recipient of a predoctoral fellowship “Ajuts 2021 de Promoció de la Recerca en Salut-9a edició” from IRBLleida/Diputació de Lleida. JD acknowledges receiving financial support from ISCIII (Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future.” MS-d-l-T has received financial support from a “Ramón y Cajal” grant (RYC2019-027831-I) from the “Ministerio de Ciencia e Innovación – Agencia Estatal de Investigación” co-funded by the European Social Fund (ESF)/“Investing in your future.” FB received funding from from ResMed (an Australian company that develops products related to sleep apnea), the Health Research Fund, the Spanish Ministry of Health, the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin (Spain), Oxigen Salud (Spain), and ALLER. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication

Medicina de precisión en pacientes con apnea obstructiva del sueño y síndrome coronario agudo

L'apnea obstructiva del son (AOS) és una malaltia crònica respiratòria molt prevalent. Es considera un problema de salut pública i un factor independent de morbiditat i mortalitat cardiovascular (CV). Tot i això, es desconeix el paper que juga en el risc de desenvolupament de malaltia CV. Les eines que proporciona la medicina de precisió podrien contribuir a caracteritzar l'heterogeneïtat de l'AOS. El primer estudi es va dirigir a explorar la relació entre l'AOS i el risc de recurrència CV en pacients amb una síndrome coronària aguda (SCA). Es va observar un efecte deleteri de l'AOS, augmentant la recurrència d'esdeveniments CV en un endotip definit per pacients admesos per un primer SCA i sense cardiopatia prèvia. El segon estudi es va centrar a identificar patrons de poligrafia respiratòria (PR) i la seva relació amb el risc de recurrència CV a l'endotip prèviament identificat. Els resultats van mostrar un patró de PR caracteritzat per hipoxèmia intermitent i associat a un risc elevat de recurrència CV en pacients amb un primer SCA sense cardiopatia prèvia. A partir d'aquests resultats, el tercer i el quart estudi es van enfocar en la caracterització dels mecanismes moleculars de recurrència CV a l'endotip de pacients amb SCA prèviament identificat. Al tercer estudi, es va identificar un perfil proteòmic específic en pacients amb SCA i AOS greu associat amb recurrència CV. Aquest perfil proteòmic constituiria una eina amb utilitat clínica per a estratificar el risc CV en pacients amb AOS. Finalment, el quart estudi va permetre identificar una empremta molecular basada en proteïnes diferencialment expressades entre pacients amb recurrència CV, amb AOS i sense. Les anàlisis d'enriquiment van mostrar la seva implicació als mecanismes de disfunció endotelial, estrès oxidatiu i inflamació sistèmica, mecanismes intermediaris que podrien ser responsables de l'associació de l'AOS i el risc de recurrència CV en pacients SCA.La apnea obstructiva del sueño (AOS) es una enfermedad crónica respiratoria muy prevalente. Se considera un problema de salud pública y un factor independiente de morbilidad y mortalidad cardiovascular (CV). No obstante, se desconoce su papel real en el riesgo de desarrollo de enfermedad CV. Las herramientas de medicina de precisión podrían contribuir a caracterizar la heterogeneidad de la AOS. El primer estudio se dirigió a explorar la relación entre la AOS y el riesgo de recurrencia CV en pacientes con un síndrome coronario agudo (SCA). Observándose un efecto deletéreo de la AOS aumentando la recurrencia de eventos CV en un endotipo definido por pacientes admitidos por un primer SCA y sin cardiopatía previa. El segundo estudio se centró en identificar patrones de poligrafía respiratoria (PR) y su relación con el riesgo de recurrencia CV en el endotipo previamente identificado. Los resultados mostraron un patrón de PR caracterizado por hipoxemia intermitente y asociado con un elevado riesgo de recurrencia CV en pacientes con un primer SCA sin cardiopatía previa. A partir de estos resultados, el tercer y cuarto estudio se enfocaron en la caracterización de los mecanismos moleculares de recurrencia CV en el endotipo de pacientes con SCA previamente identificado. En el tercer estudio, se identificó un perfil proteómico específico en pacientes con SCA y AOS grave asociado con recurrencia CV. Este perfil proteómico constituiría una herramienta con utilidad clínica para la de estratificación del riesgo CV en pacientes con AOS. Por último, el cuarto estudio permitió identificar una huella molecular basada en proteínas diferencialmente expresada entre pacientes con recurrencia CV, con y sin AOS. Los análisis de enriquecimiento mostraron su implicación en los mecanismos de disfunción endotelial, estrés oxidativo e inflamación sistémica, mecanismos intermedios que podrían ser responsables de la asociación de la AOS y el riesgo de recurrencia CV en pacientes SCA.Obstructive sleep apnea (OSA) is a highly prevalent chronic respiratory disease. It is considered a public health problem and an independent factor of cardiovascular (CV) morbidity and mortality. However, its implication on the risk of development CV disease is unknown. Precision medicine tools could help characterize the heterogeneity of OSA. The first study aimed to explore the relationship between OSA and the risk of CV recurrence in patients with acute coronary syndrome (ACS). A deleterious effect of OSA was observed, increasing the recurrence of CV events in an endotype defined by patients admitted for a first ACS and without previous heart disease. The second study focused on identifying respiratory polygraphy (RP) patterns and their relationship with the risk of CV recurrence in the previously identified endotype. The results showed a PR pattern characterized by intermittent hypoxemia and associated with a high risk of CV recurrence in patients with a first ACS without previous heart disease. Based on these results, the third and fourth studies aimed to characterize of the molecular mechanisms of CV recurrence in the previously identified endotype of ACS patients. In the third study, a specific proteomic profile was identified in patients with ACS and severe OSA associated with CV recurrence. This proteomic profile would constitute a clinically useful tool for CV risk stratification in patients with OSA. Finally, the fourth study allowed us to identify a protein-based molecular fingerprint differentially expressed between patients with CV recurrence, with and without OSA. The enrichment analyzes showed its involvement in the mechanisms of endothelial dysfunction, oxidative stress and systemic inflammation, intermediate mechanisms that could be responsible for the association of OSA and the risk of CV recurrence in ACS patients

Evaluación del metaboloma sanguíneo como herramienta para el manejo de pacientes de cáncer de mama en el contexto neoadyuvante

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 22-04-2022Esta tesis tiene embargado el acceso al texto completo hasta el 22-10-2023La posibilidad de acceder al análisis molecular de la sangre de las pacientes de cáncer de mama durante el manejo clínico rutinario abre unas enormes posibilidades para la búsqueda de nuevos marcadores con valor diagnóstico, predictivo y pronóstico en escenarios donde el análisis de la muestra tumoral no es posible, o no está indicado. El objetivo de esta tesis doctoral ha sido evaluar el potencial de la metabolómica para arrojar información sobre la evolución de las pacientes de cáncer de mama en un con- texto de neoadyuvancia. Para ello, se analizaron muestras de plasma recogidas en dis- tintos momentos (al diagnóstico, post-tratamiento y postcirugía), que fueron analiza- das mediante metabolómica y análisis computacionales. Las diferencias en las rutas metabolómicas relacionadas con la respuesta al tratamien- to son específicas de subtipo y podrían llegar a establecerse como biomarcadores de respuesta. Se observó además que los cambios en el nivel de ciertos metabolitos a lo largo del tiempo son provocados por el tratamiento, y que estos cambios no son de- pendientes de la respuesta alcanzada por las pacientes. Finalmente se identificaron dos metabolitos con capacidad de separar a las pacientes con tumores triple negativo en dos grupos, de alto y bajo riesgo, con diferente probabilidad de recaída a distancia a los tres años de la cirugía. Dichos resultados pueden suponer un pequeño avance en el establecimiento de bio- marcadores predictivos de respuesta y pronósticos, tanto para evitar terapias inefica- ces que retrasen una cirugía potencialmente curatoria, como para predecir la recaída de estas pacientes años antes de que suced